tbuckley/cabot-search huggingface dataset:
The environmental impact of the Dutch health-care sector beyond climate change: an input–output analysis
Authors: Michelle A Steenmeijer, João F D Rodrigues, Michiel C Zijp, Susanne L Waaijers-van der Loop
Journal: The Lancet Planetary Health (2022)

BackgroundStudies suggest that the Dutch health-care sector is responsible for 4–8% of the national carbon footprint, but the environmental footprint of this sector beyond climate change is not well understood. Therefore, we aimed to estimate the environmental footprint of the Dutch health-care sector for a range of environmental impact categories.MethodsIn this input–output analysis, we used Exiobase (version 3), which contains data on global trade flows and their associated environmental impact, in combination with health-care expenditure data from Statistics Netherlands. We covered the impact categories: climate change, blue water consumption, abiotic material extraction, land use, and total waste generation. The calculated sectoral footprint was the sum of all impacts associated with the operational phase (direct impact) and impacts occurring in the value chain of purchased goods and services (indirect impact) given an expenditure vector. The expenditure vector was the sum of three elements of health-care expenditure: health-care services; pharmaceuticals and chemical products; and medical appliances. We calculated the impact share of health care on the total Dutch consumption footprint. We evaluated the contribution to the impact categories from the categories that composed the expenditure vector. We did a hotspot analysis in which the indirect impact was split according to where (sector, geography, or both) the impact physically occurred. These top-down results were complemented with bottom-up data on emissions from pressurised metered-dose inhalers, anaesthetic gases, and private travel.FindingsThe health-care sector's share of the national footprint was highest for material extraction (13·0%), followed by blue water consumption (7·5%), climate change (7·3%), land use (7·2%), and waste generation (4·2%). Pharmaceuticals and other chemical products were the biggest contributors to all impacts. The sectors contributing to climate change were more evenly distributed than the sectors contributing to the other impact categories. The mining sector mostly contributed to material extraction and the agricultural sector contributed largely to blue water consumption and land use. The mining sector and the agricultural sector were the main contributors to waste generation. Climate change occurred mainly in the Netherlands, whereas the other impacts mainly occurred abroad.InterpretationThe Dutch health-care sector contributes to a broad set of environmental impact categories beyond climate change. Our results will help stakeholders involved in the health-care sector to pinpoint topics that need to be prioritised and to prevent trade-offs by addressing multiple environmental issues simultaneously.FundingDutch Ministry of Health, Welfare and Sport.
Global trends in ozone concentration and attributable mortality for urban, peri-urban, and rural areas between 2000 and 2019: a modelling study
Authors: Daniel A Malashock, Marissa N Delang, Jacob S Becker, Marc L Serre, J Jason West, Kai-Lan Chang, Owen R Cooper, Susan C Anenberg
Journal: The Lancet Planetary Health (2022)

Data on long-term trends of ozone exposure and attributable mortality across urban-rural catchment areas worldwide are scarce, especially for low-income and middle-income countries. This study aims to estimate trends in ozone concentrations and attributable mortality for urban-rural catchment areas worldwide.In this modelling study, we used a health impact function to estimate ozone concentrations and ozone-attributable chronic respiratory disease mortality for urban areas worldwide, and their surrounding peri-urban, peri-rural, and rural areas. We estimated ozone-attributable respiratory health outcomes using a modified Global Burden of Diseases, Injuries, and Risk Factors 2019 Study approach. We evaluate long-term trends with linear regressions of annual ozone concentrations and ozone-attributable mortality against time in years, and examined the influence of each health impact function input parameter to temporal changes in ozone-attributable disease burden estimates for 12 946 cities worldwide by region, from 2000 to 2019.Ozone-attributable mortality worldwide increased by 46% from 2000 (290 400 deaths [95% CI 151 800-457 600]) to 2019 (423 100 deaths [95% CI 223 200-659 400]). The fraction of global ozone-attributable mortality occurring in peri-urban areas remained unchanged from 2000 to 2019 (56%), whereas urban areas gained in their share of global ozone-attributable burden (from 35% to 37%; 54 000 more deaths). Across all cities studied, average population-weighted mean ozone concentration increased by 11% (46 parts per billion [ppb] to 51 ppb). The number of cities with concentrations above the WHO peak season ozone standard (60 μg/m3) increased from 11 568 (89%) of 12 946 cities in 2000 to 12 433 (96%) cities in 2019. Percent change in ozone-attributable mortality averaged across 11 032 cities within each region from 2000 to 2019 ranged from -62% in eastern Europe to 350% in tropical Latin America. The contribution of ozone concentrations, population size, and baseline chronic respiratory disease rates to the change in ozone-attributable mortality differed regionally.Ozone exposure is increasing worldwide, contributing to disproportionate ozone mortality in peri-urban areas and increasing ozone exposure and attributable mortality in urban areas worldwide. Reducing ozone precursor emissions in areas affecting urban and peri-urban exposure can yield substantial public health benefits.NASA Health and Air Quality Applied Sciences Team, the National Institute for Occupational Safety and Health, and the NOAA Co-operative Agreement with the Cooperative Institute for Research in Environmental Sciences.
Incorporating carbon into health care: adding carbon emissions to health technology assessments
Authors: Scott McAlister, Rachael L Morton, Alexandra Barratt
Journal: The Lancet Planetary Health (2022)

At the UN Climate Change Conference 26 in Glasgow, 50 countries committed to low-carbon health services, with 14 countries further committing to net-zero carbon health services by 2050. Reaching this target will require decision makers to include carbon emissions when evaluating new and existing health technologies (tests and treatments). There is currently, however, a scarcity of data on the carbon footprint of health-care interventions, nor any means for decision makers to include and consider carbon emission health-care assessments. We therefore investigated how to integrate carbon emissions calculated by environmental life cycle assessment (LCA) into health technology assessments (HTA). HTAs are extensively used in developing clinical and policy guidelines by individual public or private payers, and by government organisations. In the first section we explain the methodological differences between environmentally extended input-output and process-based LCA. The second section outlines ways in which carbon emissions calculated by LCA could be integrated with HTAs, recognising that HTAs are done in several ways by different jurisdictions. International effort and processes will be needed to ensure that robust and comprehensive carbon footprints of commonly used health-care products are freely available. The technical and implementation challenges of incorporating carbon emissions into HTAs are considerable, but not unsurmountable. Our aim is to lay foundations for meeting these challenges.
Challenges and shortcomings of antibacterial discovery projects
Authors: Ursula Theuretzbacher, Enrico Baraldi, Francesco Ciabuschi, Simone Callegari
Journal: Clinical Microbiology and Infection (2022)

Antibacterial drug discovery activities are essential for filling clinical pipelines with promising clinical candidates. Little information is available about the challenges and shortcomings of small companies and academic institutions in performing these important discovery tasks.We performed a content analysis of 463 reviewer comments on 91 funding applications of antibacterial drug discovery projects submitted to two major global funders between 2016 and 2020 that had not proceeded further in the selection process. This quality assessment was complemented with the inputs (via e-mail) from a panel involving six antibiotic research and development (R&D) experts with long-standing expertise and experience in antibiotic drug discovery.Common critical comments of reviewers are grouped into three main categories: scientific and technical shortcomings, unclear potential societal impact, and insufficient capability and expertise of the project team regarding the R&D process. Insufficient characterization of in vitro activity and/or testing of the hits/leads and insufficient antibacterial activity were the most common critical comments. Other areas of concern were insufficient or lack of differentiation from available drugs or projects with a long R&D history, and the research team's insufficient knowledge of a structured streamlined R&D process as reflected in severe gaps in the expertise of the R&D team. Little appreciation for the problem of the emergence of target-based resistance, especially in single-target approaches, and little awareness of toxicological issues, including approaches with historical liabilities were also commonly mentioned. The shortcomings identified through the analysis of funding applications are echoed by the results of the expert panel.Our analysis identified an urgent need of strengthening the support for antibacterial drug discovery teams to help more projects reach such a quality to be eligible for global funders and private investors.
Hospitalization for chronic obstructive pulmonary disease and pneumonia: association with the dose of inhaled corticosteroids. A nation-wide cohort study of 52 100 outpatients
Authors: Christian Rønn, Pradeesh Sivapalan, Josefin Eklöf, Peter Kamstrup, Tor Biering-Sørensen, Barbara Bonnesen, Zitta Barrella Harboe, Andrea Browatzki, Jakob Lyngby Kjærgaard, Christian Niels Meyer, Torben Tranborg Jensen, Sofie Lock Johansson, Elisabeth Bendstrup, Charlotte Suppli Ulrik, Jens-Ulrik Stæhr Jensen
Journal: Clinical Microbiology and Infection (2022)

International guidelines only advocate the use of inhaled corticosteroids (ICSs) in patients with chronic obstructive pulmonary disease (COPD) experiencing recurring exacerbations and eosinophilic inflammation. However, ICSs are commonly used in patients with COPD and without exacerbations and signs of eosinophilic inflammation, thus possibly increasing the risk of hospitalization for pneumonia. Thus, we aimed to determine the risk of hospitalization for pneumonia associated with increasing cumulated ICS doses among patients with COPD to establish whether there is dose dependency.A retrospective cohort study included all patients with COPD treated at a respiratory outpatient clinic in Denmark. The patients were divided into four groups based on their average daily ICS exposure. The dose-response relationship was investigated using a multivariable Cox proportional hazard regression analysis.In total, 52 100 patients were included, who were divided into the no-use (n = 15 755), low-dose (n = 12 050), moderate-dose (n = 12 488), and high-dose (n = 11 807) groups. ICS use was strongly associated with hospitalization for pneumonia (hazard ratio [HR], 1.3; CI, 1.2-1.3) (ICS vs. no ICS). The risk of hospitalization for pneumonia increased with every dosing group step: low dose: HR, 1.1 (CI, 1.0-1.2); moderate dose: HR, 1.2 (CI, 1.1-1.3), and high dose: HR, 1.5 (CI, 1.4-1.6); "no use" was the reference. Sensitivity analyses confirmed these findings.In the dose-response relationship analysis, ICS dose were associated with a substantially increased risk of hospitalization for pneumonia of up to 50%. Our data support that ICSs should be administered at the lowest possible dose and only to patients with COPD who have a documented need.
Chymase-1: a “MAST”-er switch in COPD?
Authors: Corrine R. Kliment, Reinoud Gosens
Journal: European Respiratory Journal (2022)

Chronic inflammation of the airways and lung tissue is an important feature of COPD. In recent years, a role for mast cells has emerged in numerous diseases, including COPD [1–4]. Mast cells are long-lived tissue-resident immune cells that secrete proteases and chymases (such as CMA1), interact with antigen-presenting cells and mediate immune responses [5]. These granule-filled cells were first described by Ehrlich [6] in 1878. The role of mast cells in lung disease has been shown in asthma [7], but remains relatively unexplored in COPD. In patients with COPD, there are changes in the density and localisation of tissue-resident mast cells [1, 2, 4, 8]. Mast cells are emerging as an important cell type in the chronic inflammation present in COPD and are poised to be the focus of future therapeutic approaches. <https://bit.ly/3yotNbW>
The<i>SOX17</i>phenotype in pulmonary arterial hypertension: lessons for pathobiology and clinical management
Authors: Jurjan Aman, Nicholas W. Morrell, Christopher J. Rhodes, Martin R. Wilkins, Harm Jan Bogaard
Journal: European Respiratory Journal (2022)

Worldwide collaborative efforts to understand the genetic architecture of pulmonary arterial hypertension (PAH) have identified several gene variants and mutations in the past 5 years. With subsequent deep phenotyping, the clinical picture associated with these mutations is becoming more clear. For example, following the identification of pathogenic mutations in TBX4 and KDR [1, 2], histopathological and clinical phenotypes were described, with specific characteristics like small patella and bronchial diverticulosis for TBX4 and low diffusing capacity of the lung for carbon monoxide and interstitial changes for KDR [3–5]. Just as mutations identify key players in pathophysiology, the clinical and histopathological characterisation of mutation carriers provides insights into the cellular processes involved. SOX17 mutations in pulmonary arterial hypertension: phenotype and pathophysiological considerations <https://bit.ly/3R7VVHw>
Flexible sensory-motor mapping rules manifest in correlated variability of stimulus and action codes across the brain
Authors: Ruud L. van den Brink, Keno Hagena, Niklas Wilming, Peter R. Murphy, Christian Büchel, Tobias H. Donner
Journal: Neuron (2022)

Humans and non-human primates can flexibly switch between different arbitrary mappings from sensation to action to solve a cognitive task. It has remained unknown how the brain implements such flexible sensory-motor mapping rules. Here, we uncovered a dynamic reconfiguration of task-specific correlated variability between sensory and motor brain regions. Human participants switched between two rules for reporting visual orientation judgments during fMRI recordings. Rule switches were either signaled explicitly or inferred by the participants from ambiguous cues. We used behavioral modeling to reconstruct the time course of their belief about the active rule. In both contexts, the patterns of correlations between ongoing fluctuations in stimulus- and action-selective activity across visual- and action-related brain regions tracked participants' belief about the active rule. The rule-specific correlation patterns broke down around the time of behavioral errors. We conclude that internal beliefs about task state are instantiated in brain-wide, selective patterns of correlated variability.
Hypothalamic warm-sensitive neurons require TRPC4 channel for detecting internal warmth and regulating body temperature in mice
Authors: Qian Zhou, Xin Fu, Jianhui Xu, Shiming Dong, Changhao Liu, Dali Cheng, Cuicui Gao, Minhua Huang, Zhiduo Liu, Xinyan Ni, Rong Hua, Hongqing Tu, Hongbin Sun, Qiwei Shen, Baoting Chen, Jin Zhang, Liye Zhang, Haitao Yang, Ji Hu, Wei Yang, Weihua Pei, Qiyuan Yao, Xing Sheng, Jie Zhang, Wen Z. Yang, Wei L. Shen
Journal: Neuron (2022)
Mendelian Randomization Implicates Bidirectional Association between Myopia and Primary Open-Angle Glaucoma or Intraocular Pressure
Authors: Rachel S. Chong, Hengtong Li, Alex J.Y. Cheong, Qiao Fan, Victor Koh, Lavanya Raghavan, Monisha E. Nongpiur, Ching-Yu Cheng
Journal: Ophthalmology (2022)
Genomic Shift in Population Dynamics of <i>mcr</i>-<i>1</i>-Positive <i>Escherichia Coli</i> in Human Carriage
Authors: Yingbo Shen, Rong Zhang, Dongyan Shao, Lu Yang, Jiayue Lu, Congcong Liu, Xueyang Wang, Junyao Jiang, Boxuan Wang, Congming Wu, Julian Parkhill, Yang Wang, Timothy R. Walsh, George F. Gao, Zhangqi Shen
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract Emergence of the colistin resistance gene, mcr-1, has attracted worldwide attention. Despite the prevalence of mcr-1-positive Escherichia coli (MCRPEC) strains in human carriage showing a significant decrease between 2016 and 2019, genetic differences in MCRPEC strains remain largely unknown. We therefore conducted a comparative genomic study on MCRPEC strains from fecal samples of healthy human subjects in 2016 and 2019. We identified three major differences in MCRPEC strains between these two time points. First, the insertion sequence ISApl1 was often deleted and the percentage of mcr-1-carrying IncI2 plasmids was increased in MCRPEC strains in 2019. Second, the antibiotic resistance genes (ARGs), aac(3)-IVa and blaCTX-M-1, emerged and coexisted with mcr-1 in 2019. Third, MCRPEC strains in 2019 contained more virulence genes, resulting in an increased proportion of extraintestinal pathogenic E. coli (ExPEC) strains (36.1%) in MCRPEC strains in 2019 compared to that in 2016 (10.5%), implying that these strains could occupy intestinal ecological niches by competing with other commensal bacteria. Our results suggest that despite the significant reduction in the prevalence of MCRPEC strains in humans from 2016 to 2019, MCRPEC exhibits increased resistance to other clinically important ARGs and contains more virulence genes, which may pose a potential public health threat.
Corrigendum to “Mussel-inspired nanozyme catalyzed conductive and self-setting hydrogel for adhesive and antibacterial bioelectronics” [Bioact. Mater. 6 (2021) 2676–2687 / 452]
Authors: Zhanrong Jia, Xuanhan Lv, Yue Hou, Kefeng Wang, Fuzeng Ren, Dingguo Xu, Qun Wang, Kelong Fan, Chaoming Xie, Xiong Lu
Journal: Bioactive Materials (2022)

[This corrects the article DOI: 10.1016/j.bioactmat.2021.01.033.].
Molecular Biomarkers of Disease Outcomes and Mechanisms of Acquired Resistance to First-Line Osimertinib in Advanced EGFR-Mutant Lung Cancers
Authors: Noura J. Choudhury, Antonio Marra, Jane S.Y. Sui, Jessica Flynn, Soo-Ryum Yang, Christina J. Falcon, Pier Selenica, Adam J. Schoenfeld, Natasha Rekhtman, Daniel Gomez, Michael F. Berger, Marc Ladanyi, Maria Arcila, Charles M. Rudin, Gregory J. Riely, Mark G. Kris, Glenn Heller, Jorge S. Reis-Filho, Helena A. Yu
Journal: Journal of Thoracic Oncology (2022)
CNEReg Interprets Ruminant-Specific Conserved Non-Coding Elements by Developmental Gene Regulatory Network
Authors: Xiangyu Pan, Zhaoxia Ma, Xinqi Sun, Hui Li, Tingting Zhang, Chen Zhao, Nini Wang, Rasmus Heller, Wing Hung Wong, Wen Wang, Yu Jiang, Yong Wang
Journal: Genomics Proteomics & Bioinformatics (2022)

Abstract The genetic information coded in DNA leads to trait innovation via a gene regulatory network (GRN) in development. Here, we developed a conserved non-coding element interpretation method to integrate multi-omics data into gene regulatory network (CNEReg) to investigate the ruminant multi-chambered stomach innovation. We generated paired expression and chromatin accessibility data during rumen and esophagus development in sheep, and revealed 1601 active ruminant-specific conserved non-coding elements (active-RSCNEs). To interpret the function of these active-RSCNEs, we defined toolkit transcription factors (TTFs) and modeled their regulation on rumen-specific genes via batteries of active-RSCNEs during development. Our developmental GRN revealed 18 TTFs and 313 active-RSCNEs regulating 7 rumen functional modules. Notably, 6 TTFs (OTX1, SOX21, HOXC8, SOX2, TP63, and PPARG), as well as 16 active-RSCNEs, functionally distinguished the rumen from the esophagus. Our study provides a systematic approach to understanding how gene regulation evolves and shapes complex traits by putting evo-devo concepts into practice with developmental multi-omics data.
Cooling Device to Prevent Chemotherapy Oral Mucositis Gains Authorization
Authors: Howard D. Larkin
Journal: JAMA (2022)

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Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes
Authors: Revathi Sekar, Karsten Motzler, Yun Kwon, Aaron Novikoff, Julia Jülg, Bahar Najafi, Surui Wang, Anna-Luisa Warnke, Susanne Seitz, Daniela Hass, Sofiya Gancheva, Sabine Kahl, Bin Yang, Brian Finan, Kathrin Schwarz, Juergen G. Okun, Michael Roden, Matthias Blüher, Timo D. Müller, Natalie Krahmer, Christian Behrends, Oliver Plettenburg, Marta Miaczynska, Stephan Herzig, Anja Zeigerer
Journal: Cell Metabolism (2022)

(Cell Metabolism 34, 1–19.e1–e9; November 1, 2022) Due to a typesetter error, the originally published version of this article was missing asterisks in Figure 1D, indicating 3-star significance for the comparison of VPS37A transcript levels in CTR versus obese. This error has now been corrected online. The error does not affect any conclusions in the paper. The journal apologizes for the error and any confusion it may have caused.Figure 1D. Depletion of Vps37a in liver causes increased glucose production and activation of the basal cAMP/PKA/p-Creb pathway (original)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomesSekar et al.Cell MetabolismOctober 14, 2022In BriefSekar et al. report on a novel mechanism to uncouple differential signaling outcomes of the glucagon receptor in the liver. Changing the localization of the receptor by targeting endosomal Vps37a alters glucose production and usage downstream of glucagon, without affecting lipid metabolism. Full-Text PDF Open Access
Alcohol Abstinence Improves Prognosis Across All Stages of Portal Hypertension in Alcohol-Related Cirrhosis
Authors: Benedikt Silvester Hofer, Benedikt Simbrunner, Lukas Hartl, Mathias Jachs, David Josef Maria Bauer, Lorenz Balcar, Rafael Paternostro, Philipp Schwabl, Georg Semmler, Bernhard Scheiner, Albert Friedrich Staettermayer, Michael Trauner, Mattias Mandorfer, Thomas Reiberger
Journal: Clinical Gastroenterology and Hepatology (2022)
Advances in Single-component inorganic nanostructures for photoacoustic imaging guided photothermal therapy
Authors: Houjuan Zhu, Bofan Li, Chui Yu Chan, Beverly Low Qian Ling, Jiaqian Tor, Xin Yi Oh, Wenbin Jiang, Enyi Ye, Zibiao Li, Xian Jun Loh
Journal: Advanced Drug Delivery Reviews (2022)